Circular RNA as a potential diagnostic and/or therapeutic target for endometriosis

Endometriosis is a pathology form of endometrium that behaves in a similar way to malignancies, such as invasion and resistance to apoptosis. Circular RNAs (CircRNAs) are a class of noncoding RNAs that have several biological functions including, miRNA sponging, sequestering of proteins, enhancing parental gene expression and translation resulting in polypeptides. In this review, we highlighted the roles of circRNAs as potential diagnostic and therapeutic biomarkers in endometriosis. Moreover, we summarized the roles of circRNAs in the pathogenesis of endometriosis via different signaling pathways, such as the miRNA network and apoptosis.

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Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression

BioMed Research International ◽

10.1155/2020/3589871 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Huijie Gu ◽

Xiangyang Cheng ◽

Jun Xu ◽

Kaifeng Zhou ◽

Chong Bian ◽

...

Keyword(s):

Gene Expression ◽

Cancer Progression ◽

Therapeutic Target ◽

Critical Role ◽

Noncoding Rnas ◽

Circular Rna ◽

Expression Level ◽

Circular Rnas ◽

Competing Endogenous Rna ◽

Potential Therapeutic Target

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

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A novel circular RNA, circXPO1, promotes lung adenocarcinoma progression by interacting with IGF2BP1

Cell Death and Disease ◽

10.1038/s41419-020-03237-8 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Qi Huang ◽

Haifa Guo ◽

Shaodong Wang ◽

Yi Ma ◽

Haiming Chen ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Therapeutic Target ◽

Noncoding Rnas ◽

Xenograft Model ◽

Gene Copy Number ◽

Circular Rna ◽

Gene Copy ◽

Circular Rnas ◽

Functional Roles ◽

Tumor Tissues

AbstractStudies have demonstrated that noncoding RNAs play important roles in various types of cancer; however, noncoding RNAs derived from regions of genomic alterations have rarely been explored, especially for circular RNAs (circRNA). Previously, we found several circRNAs were upregulated in lung adenocarcinoma (LUAD) tumor tissues by RNA sequencing. Here, we characterized a novel circRNA, circXPO1, in LUAD, which is derived from a well-established cancer therapeutic target, XPO1. circXPO1, is formed by back-splicing of exon 3 and exon 4 of XPO1 gene. circXPO1 was highly expressed in LUAD tissues compared with paired adjacent non-tumor tissues, and high circXPO1 expression correlated with worse overall survival. circXPO1 expression was positively correlated with the XPO1 gene copy number. Mechanically, circXPO1 could bind with IGF2BP1 and enhance CTNNB1 mRNA stability, and subsequently promote LUAD progression. In a LUAD patient-derived xenograft model, intratumoural injection of cholesterol-conjugated siRNA specifically targeting circXPO1 efficiently suppressed tumor growth. To summary, these results suggest that circXPO1 is critical for LUAD progression and may serve as a biomarker for poor prognosis and a therapeutic target. On the other hand, the functional roles of noncoding transcripts derived from coding genes should be re-evaluated.

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Cancer-related circular RNA: diverse biological functions

Cancer Cell International ◽

10.1186/s12935-020-01703-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dan Cheng ◽

Jing Wang ◽

Zigang Dong ◽

Xiang Li

Keyword(s):

Noncoding Rnas ◽

Circular Rna ◽

Long Noncoding Rnas ◽

Circular Rnas ◽

Biological Functions ◽

Diagnosis Of Cancer ◽

The Relationship ◽

Potential Biomarkers

AbstractNoncoding RNAs, including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in regulating biological functions. In recent decades, miRNAs and lncRNAs have both inspired a wave of research, but the study of circRNA functions is still in its infancy. Studies have found that circRNAs actively participate in the occurrence and development of various diseases, which emphasizes the importance of circRNAs. Here, we review the features and classification of circRNAs and summarize their functions. Then, we briefly describe how to analyze circRNAs by bioinformatics procedures. In addition, the relationship between circRNAs and cancers is discussed with an emphasis on proving whether circRNAs can be potential biomarkers for the prognosis and diagnosis of cancer.

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Comparative Analysis of Gammaherpesvirus Circular RNA Repertoires: Conserved and Unique Viral Circular RNAs

Journal of Virology ◽

10.1128/jvi.01952-18 ◽

2018 ◽

Vol 93 (6) ◽

Cited By ~ 7

Author(s):

Nathan A. Ungerleider ◽

Vaibhav Jain ◽

Yiping Wang ◽

Nicholas J. Maness ◽

Robert V. Blair ◽

...

Keyword(s):

Rhesus Macaque ◽

Noncoding Rnas ◽

Circular Rna ◽

Circular Rnas ◽

Infection Model ◽

Host Immune System ◽

Immune Recognition ◽

Origin Of Replication ◽

Two Samples ◽

Virus Biology

ABSTRACTRecent studies have identified circular RNAs (circRNAs) expressed from the Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV) human DNA tumor viruses. To gain initial insights into the potential relevance of EBV circRNAs in virus biology and disease, we assessed the circRNAome of the interspecies homologue rhesus macaque lymphocryptovirus (rLCV) in a naturally occurring lymphoma from a simian immunodeficiency virus (SIV)-infected rhesus macaque. This analysis revealed rLCV orthologues of the latency-associated EBV circular RNAs circRPMS1_E4_E3a and circEBNA_U. Also identified in two samples displaying unusually high lytic gene expression was a novel rLCV circRNA that contains both conserved and rLCV-specific RPMS1 exons and whose backsplice junctions flank an rLCV lytic origin of replication (OriLyt). Analysis of a lytic infection model for the murid herpesvirus 68 (MHV68) rhadinovirus identified a cluster of circRNAs near an MHV68 lytic origin of replication, with the most abundant of these, circM11_ORF69, spanning the OriLyt. Lastly, analysis of KSHV latency and reactivation models revealed the latency associated circRNA originating from the vIRF4 gene as the predominant viral circRNA. Together, the results of this study broaden our appreciation for circRNA repertoires in theLymphocryptovirusandRhadinovirusgenera of gammaherpesviruses and provide evolutionary support for viral circRNA functions in latency and viral replication.IMPORTANCEInfection with oncogenic gammaherpesviruses leads to long-term viral persistence through a dynamic interplay between the virus and the host immune system. Critical for remodeling of the host cell environment after the immune responses are viral noncoding RNAs that modulate host signaling pathways without attracting adaptive immune recognition. Despite the importance of noncoding RNAs in persistent infection, the circRNA class of noncoding RNAs has only recently been identified in gammaherpesviruses. Accordingly, their roles in virus infection and associated oncogenesis are unknown. Here we report evolutionary conservation of EBV-encoded circRNAs determined by assessing the circRNAome in rLCV-infected lymphomas from an SIV-infected rhesus macaque, and we report latent and lytic circRNAs from KSHV and MHV68. These experiments demonstrate utilization of the circular RNA class of RNAs across 4 members of the gammaherpesvirus subfamily, and they identify orthologues and potential homoplastic circRNAs, implying conserved circRNA functions in virus biology and associated malignancies.

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The Regulatory Functions of Circular RNAs in Digestive System Cancers

Cancers ◽

10.3390/cancers12030770 ◽

2020 ◽

Vol 12 (3) ◽

pp. 770 ◽

Cited By ~ 4

Author(s):

Xiao Yuan ◽

Ya Yuan ◽

Zhi He ◽

Diyan Li ◽

Bo Zeng ◽

...

Keyword(s):

Digestive System ◽

Rna Binding ◽

Rna Binding Proteins ◽

Circular Rna ◽

Research Progress ◽

Circular Rnas ◽

Biological Functions ◽

Ribonucleic Acids ◽

Mirna Sponges ◽

And Biological Markers

Circular ribonucleic acids (circRNAs), which are a type of covalently closed circular RNA, are receiving increasing attention. An increasing amount of evidence suggests that circRNAs are involved in the biogenesis and development of multiple diseases such as digestive system cancers. Dysregulated circRNAs have been found to act as oncogenes or tumour suppressors in digestive system cancers. Moreover, circRNAs are related to ageing and a wide variety of processes in tumour cells, such as cell apoptosis, invasion, migration, and proliferation. Moreover, circRNAs can perform a remarkable multitude of biological functions, such as regulating splicing or transcription, binding RNA-binding proteins to enable function, acting as microRNA (miRNA) sponges, and undergoing translated into proteins. However, in digestive system cancers, circRNAs function mainly as miRNA sponges. Herein, we summarise the latest research progress on biological functions of circRNAs in digestive system cancers. This review serves as a synopsis of potential therapeutic targets and biological markers for digestive system cancer.

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Research Status of Differentially Expressed Noncoding RNAs in Type 2 Diabetes Patients

BioMed Research International ◽

10.1155/2020/3816056 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Rou Shi ◽

Yingjian Chen ◽

Yuanjun Liao ◽

Rang Li ◽

Chunwen Lin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Signaling Pathways ◽

Insulin Signaling ◽

Target Genes ◽

Mononuclear Cells ◽

Noncoding Rnas ◽

Vascular Complications ◽

Differentially Expressed ◽

Circular Rnas

Aims. Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. Methods. The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA–miRNA and circRNA–miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE–RAGE signaling pathways of diabetic complications. Results. A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE–RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE–RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. Conclusion. Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.

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Gammaherpesvirus RNAs Come Full Circle

mBio ◽

10.1128/mbio.00071-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 3

Author(s):

Nathan A. Ungerleider ◽

Scott A. Tibbetts ◽

Rolf Renne ◽

Erik K. Flemington

Keyword(s):

Adaptive Immune Response ◽

Noncoding Rnas ◽

Viral Gene Expression ◽

Circular Rna ◽

Circular Rnas ◽

Viral Gene ◽

Functional Studies ◽

Barr Virus ◽

Epstein Barr ◽

Gammaherpesvirus 68

ABSTRACTAfter an adaptive immune response is mounted, gammaherpesviruses achieve persistence through the utilization of viral noncoding RNAs to craft a suitable host cell environment in an immunologically transparent manner. While gammaherpesvirus long noncoding RNAs (lncRNAs) and microRNAs have been recognized for some time and have been actively investigated, a recent spate of reports have now identified repertoires of the circular RNA (circRNA) class of noncoding RNAs in both the lymphocryptovirus and rhadinovirus genera of gammaherpesviruses. Despite the recent nature of these findings, the detection of circRNAs across viruses and viral gene expression programs, the conservation of some viral circRNAs, and their detection in the clinical setting already raises the spectrum of functional importance in gammaherpesvirus biology and associated malignancies. Here, we provide an overview of currently known gammaherpesvirus circular RNAs and discuss reported physical and contextual properties that may be germane to future functional studies. With the Epstein-Barr virus (EBV) circRNAome being the most extensively studied to date, our discussions will be weighted toward EBV circRNAs while also addressing circRNAs discovered in the rhesus macaque lymphocryptovirus (rLCV), the Kaposi’s sarcoma herpesvirus (KSHV), and the murid gammaherpesvirus 68 (MHV68). We hope that this will help set the stage for future investigations into the functions and relevance of this new class of viral noncoding RNAs in infection and disease.

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Circular RNAs in Cardiovascular Disease: An Overview

BioMed Research International ◽

10.1155/2017/5135781 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 66

Author(s):

Ximin Fan ◽

Xinyu Weng ◽

Yifan Zhao ◽

Wei Chen ◽

Tianyi Gan ◽

...

Keyword(s):

Gene Expression ◽

Cardiovascular Disease ◽

Cardiovascular Diseases ◽

Noncoding Rna ◽

Essential Role ◽

Closed Loop ◽

Regulation Of Gene Expression ◽

Circular Rna ◽

Circular Rnas ◽

Mirna Sponges

Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.

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N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.709299 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jun Wu ◽

Xin Guo ◽

Yi Wen ◽

Shangqing Huang ◽

Xiaohui Yuan ◽

...

Keyword(s):

Cellular Localization ◽

Circular Rna ◽

Regulatory Mechanisms ◽

Circular Rnas ◽

Biological Functions ◽

Future Directions ◽

Rna Molecules ◽

Physiological Processes ◽

Rna Biology ◽

Insight Into

As the most abundant internal modification in eukaryotic cells, N6-methyladenosine (m6A) in mRNA has shown widespread regulatory roles in a variety of physiological processes and disease progressions. Circular RNAs (circRNAs) are a class of covalently closed circular RNA molecules and play an essential role in the pathogenesis of various diseases. Recently, accumulating evidence has shown that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNA metabolism, including biogenesis, translation, degradation and cellular localization. Through regulating circRNAs, studies have shown the important roles of m6A modification in circRNAs during immunity and multiple diseases, which represents a new layer of control in physiological processes and disease progressions. In this review, we focused on the roles played by m6A in circRNA metabolism, summarized the regulatory mechanisms of m6A-modified circRNAs in immunity and diseases, and discussed the current challenges to study m6A modification in circRNAs and the possible future directions, providing a comprehensive insight into understanding m6A modification of circRNAs in RNA epigenetics.

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circSLC30A7 Inhibits Hepatocellular Carcinoma Cell Proliferation via the miR-767-5p/FBXW7/NOTCH1 Axis

Journal of Oncology ◽

10.1155/2021/8800657 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Xiaotian Yu ◽

Yun Zhang ◽

Chao Jiang ◽

Feng Zhan ◽

Zhenwei Shen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Carcinoma Cell ◽

Noncoding Rnas ◽

Human Tumor ◽

Circular Rnas ◽

Biological Functions ◽

Research Fields ◽

Tumor Research ◽

Microrna Sponges

Circular RNAs, noncoding RNAs, have attracted much attention in various human tumor research fields. They regulate the development of various human cancers via microRNA sponges. This study aimed to assess the molecular mechanism of circSLC30A7 in hepatocellular carcinoma (HCC). In our study, we identified that circSLC30A7 was significantly downregulated in HCC cell lines and tissues. Furthermore, gain and loss function experiments were conducted to elucidate the biological functions of circSLC30A7 in HCC cell lines. Mechanistically, circSLC30A7 sponged miR-767-5p, inhibiting the expression of its downstream protein, FBXW7. In summary, this study revealed that circSLC30A7 is an essential tumor suppressor that inhibits HCC tumorigenesis through the miR-767-5p/FBXW7/NOTCH1 axis. Taken together, circSLC30A7 reduces HCC malignancy and can be a biomarker for HCC management.

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